A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Failure of Ixodes ticks to inherit Borrelia afzelii infection

To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Diagnostic value of nasal provocation testing and rhinomanometry in allergic rhinitis

Assessment of the hemodynamic and anatomic results following balloon angioplasty of discrete native coarctation of the aorta, with particular attention to "remodeling," has required repeat cardiac catheterization and angiography, which is invasive and has limited resolution. Eight patients with hypertension and discrete native coarctation with an otherwise normally developed aortic arch underwent angioplasty at 5.0 +/- 6.8 years of age. Angiographic cross-sectional areas of the aorta indexed to body surface area at the isthmus (I), coarctation site (C), and 1 cm distal to the coarctation site (Cd) pre- and postangioplasty were compared with MRI-indexed cross-sectional areas 18 +/- 10 months (MRI-1) and 35 +/- 11 months (MRI-2) postangioplasty. From preangioplasty to MRI-2, the isthmus was smaller (149 +/- 22 versus 127 +/- 27 mm2/m2; p < 0. 05). The coarctation site was larger postangioplasty (25 +/- 9 versus 116 +/- 40 mm2/m2; p < 0.001) with continued growth at latest follow-up (116 +/- 40 versus 164 +/- 36 mm2/m2; p < 0.01). The segment 1 cm distal to the coarctation site continued to decrease in area at latest follow-up (267 +/- 78 versus 163 +/- 38 mm2/m2; p < 0. 001). I versus C versus Cd at MRI-2 were similar, whereas postangioplasty and MRI-1 cross-sectional area measurements were significantly different. Following angioplasty of discrete native coarctation, the aorta becomes more uniform or undergoes "remodeling." Noninvasive MRI is an effective means of evaluating the anatomic result following balloon angioplasty, obviating the need for repeated invasive cardiac catheterizations.     

Obturation of a C-shaped canal using an improved method of warm lateral condensation

Pilot studies conducted by the authors seem to indicate that obturation of a root canal system by the lateral condensation of gutta-percha using an electrically heated spreader results in a more homogeneous mass of gutta-percha than standard lateral condensation. This article describes an improved variation which prevents inadvertent dislodgement of the mass of gutta-percha during the obturation. The authors refer to this technique as "zap and tap" and a case report describes its use to obturate a C-shaped canal system of a mandibular second molar.     

Immunogenicity of a Salmonella typhi CVD 908 candidate vaccine strain expressing the major surface protein gp63 of Leishmania mexicana mexicana

Attenuated Salmonella typhi are attractive for use as live vector vaccines to express protozoal antigens and deliver them to the human immune system. The gene encoding the mature form of Leishmania mexicana mexicana gp63 under control of tac promoter was integrated into the delta aroC locus of the chromosome of attenuated delta aroC, delta aroD S. typhi strain CVD 908. After oral immunization of BALB/c mice with two 1 x 10(9) colony forming unit doses given 21 days apart, CVD 908 omega (delta aroC::Ptac-gp63) elicited a broad T cell-mediated immune response against L. m. mexicana gp63 as demonstrated by: (1) lymphoproliferative response to fixed whole L. m. mexicana promastigotes; (2) activation of IL-2 (but not IL-4)-producing lymphocytes; (3) appearance of cytotoxic T cells against mouse mastocytoma cells expressing gp63. This T-cell mediated immune response was associated with significant protection in F1 (BALB/cXC57Bl/6) mice challenged in their footpads with a wild type strain of L. m. mexicana.     

Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells

We describe a collective episode of psychogenic illness in an indigenous group (Embera) of Colombia, geographically isolated from its native homeland and surrounded by non-indigenous settlers. The condition, which affected three young adult men and six adolescent women, was attributed by them to a spell (maleficio). It was designated as ataques de locura (madness attacks) according to their traditional medical system; and as a conversive disorder with dissociative features by psychiatrists. Different therapeutic approaches, including antipsychotic medication, religious healers and traditional herbal remedies were unsuccessful. Contact with shamans of the same ethnic origin, on the other hand, proved to be an effective way of dealing with the symptoms. We interpret the situation as an expression of psychosocial stress secondary to cultural change. This medical problem bears close resemblance to other specific culture-bound syndromes such as ataques de nervios or possession syndromes and gives clues to ways of dealing with psychogenic expressions of cultural stress.     

Detection of coronary stenoses on source and projection images using three-dimensional MR angiography with retrospective respiratory gating: preliminary experience

OBJECTIVE: Our objective was to study the ability of three-dimensional MR angiography with retrospective respiratory gating to reveal stenoses in proximal coronary arteries on source and projection images. CONCLUSION: Proximal coronary artery stenoses can be identified using three-dimensional MR angiography with retrospective respiratory gating, both with projection images and on source images alone. Reasons for missed lesions included collateral vessels and retrograde flow distal to complete occlusion and volume averaging of vessels with adjacent structures. Causes of false-positive interpretations included small foci of decreased signal intensity distal to complete occlusion, partial volume effects on individual partitions, and regions of distal vessels leaving the imaging plane.